Experiments have been undertaken for a long time on administering pharmaceuticals and other active agents in sufficient doses by transdermal application. In many cases this would save patients an injection that is often annoying, painful and connected with the risk of infection, and, on the other hand, it could avoid oral application that is often annoying, difficult to control and almost impossible in the case of some medications.
Transdermal application has a series of advantages, especially in the case of children who are afraid of injections, and who are reluctant to take medications orally because of their bad taste, in the case of the chronically ill and in the case of geriatric patients.
Without additional measures, in the case of most substances, only a very small quantity of active agent can be absorbed through the skin per unit of time. The reason is that the skin represents, by its nature, a very effective permeation barrier for protecting the body from infections and environmental toxins.
For this reason, active agents that are to be administered through the skin have to be applied to the skin in large doses. As a rule, above all, those active agents are suitable for transdermal application which are to develop their action in close proximity to the place of application, in order to treat, for instance, inflammations or allergic reactions.
Only in a few cases can active agents, applied in that manner, get into the blood circulation in sufficient quantity, and develop a systemic effect. This approach is reserved for active agents which are able comparatively easily to penetrate the skin because of their size and their molecular character, or which have to be administered in extremely small doses.
Lipophilic substances, as a rule, are easily able to penetrate the upper skin layer (the stratum corneum). However, they are subsequently taken up into the blood only with difficulty, since doing this, in turn, requires hydrophilic properties. Therefore, in the case of direct transdermal application, it is necessary to formulate the substances in such a way that they are both sufficiently lipophilic and hydrophilic. Examples of substances successfully applicable via the skin are sex hormones, nicotine and scopolamine.
To improve the transdermal passage of the active agents, there are several approaches to reducing the barrier function of the skin for a time period of greater or lesser length. This may involve laserporation, ultrasound, iontophoresis, electroporation, liquid jets, powder jets or chemical supports. All approaches have their individual disadvantages and limitations. The first named are not established, so that, up to now, only the chemical supports (e.g. dimethylsulfoxide) are used to a greater extent.
A different approach falling under this category is the use of microneedles, with whose help the stratum corneum of the skin is penetrated. The microneedles are frequently situated in the form of arrays. The needles are subsequently removed, a plaster containing active agents is applied externally, and the active agents released by it are then able to pass through the skin more easily.
In this manner, a diffusion rate through the skin of the active agents, that is increased by several orders of magnitude (103-109), is achieved, and new active agents for transdermal application can be developed.
Microneedle arrays for this purpose are discussed, for example, in U.S. Pat. No. 6,334,856.
However, this approach also has a series of disadvantages. For instance, the taking up of the active agent by the microinjuries brought about is poorly defined, since the size of the permeations generated and the complete healing rate, and thus the rate of reclosure, are individually different. Thus, the administered dose is hard to determine. Moreover, the microinjuries that are generated make possible the passage through the skin of infective agents. Consequently, the method involves a considerable risk of infection.
Microneedle arrays are known in the related art which remain in the skin during the application of the medication. The microneedles have a porous structure and/or a central channel in order to be passable to the pharmaceuticals, toxins or active agents applied from the outside. Such arrays are discussed, for example, in U.S. Pat. No. 6,908,453, and in U.S. Published Patent Applications Nos. 2006/030812 and 2005/261632.
Beyond this, U.S. Pat. No. 7,770,480 explains that the microneedles can be produced from microporous silicon which, on the one hand, makes possible the passage of the active agents and, on the other hand, has biocompatible properties.
It is a disadvantage of all the arrays that they have to be removed again after the therapy, open microinjuries being produced by this which make possible the passage of infective agents through the skin as well. Consequently, the method involves a considerable risk of infection. Besides, handling is made more complicated by the need to remove the array again. Furthermore, there is the danger that parts of the microneedles break off and remain in the body, and are rejected by the immune system if no material is used that is easily broken down by the body.